Calcium-Channel Blockers

Prescribed to treat Htn, angina, supraventricular arrhythmias, cerebral vasospasm, and HCM.

CCBs are used chronically in a significant proportion of the surgical population. CCBs are utilized in the treatment of Htn, CAD, or supraventricular arrhythmias and syndromes associated with vascular spasm. CCBs are recommended in combination with ACE inhibitors for diabetic pts with Htn. This class of drug effectively decreases myocardial O ₂ demand through its effects on AV conduction, inotropy, and vasodilatation of systemic and coronary vasculature. The dihydropyridine class of CCB given as a single agent has been associated with tachycardia.

Hypotension: A meta-analysis of both cardiac and noncardiac RCTs shows a 50% increase in the incidence of unplanned periop hypotension.

Neither RCTs nor nonrandomized trials have demonstrated an increased incidence of CHF or the need for inotropic support.

AV nodal block or asystole has not been demonstrated; however, there is increased utilization of temporary cardiac pacing after cardiac surgery. Bradycardia requiring treatment has been demonstrated in a frequency similar to beta blockers.

In both cardiac and noncardiac surgery, beneficial effects have been demonstrated; acute withdrawal can precipitate acute coronary ischemia.

One large nonrandomized study has associated dihydropyridines with increased mortality.

Neither meta-analyses nor nonrandomized trials have demonstrated any hematologic effects.

Ca ²⁺ channels: Functional pores in cardiac and smooth muscle cell membranes allow calcium to flow down an electrochemical gradient. Channels are also present in sarcoplasmic reticulum and mitochondria. Calcium is a primary generator of the cardiac action potential and intracellular events regulating muscular contraction.

Calcium enters through voltage-dependent or receptor-operated channels. Most of the effects of calcium channel blockers are regulated by components of the L (long-lasting) type receptor.

Amlodipine is the most widely prescribed calcium channel blocker; has a half-life of 30–50 hr and bioavailability of 60–90%; it is predominately metabolized to inactive metabolites and excreted in urine.

Verapamil: 90% absorbed PO, 20-35% bioavailability, onset of action 2 h, peak effect of IV/PO 3-4 h, 85% eliminated by first-pass hepatic metabolism with elimination T½ 3-7 h; IV effects almost immediate.

Diltiazem: 89–90% PO absorption,40–70% bioavailability, PO onset of action <15 min, peak effect 30 min, 60% metabolized by liver, remainder excreted by kidneys, T _½ 3.5–6.0 h.

Bepridil: >90% absorption, >80% bioavailability, PO onset of action 2–3 h, peak effect within 8 h, hepatic elimination with T _½ 26–64 h.

Hepatic disease may necessitate decreased dosing of verapamil and other CCBs.